Medical Device Daily Washington Editor

WASHINGTON — The path from basic science to the bedside has never been quickly and easily traversed, but the recent emphasis on translational research (TR) underscores the fact that it has become more arduous and expensive.

This is the dilemma addressed during a session sponsored by the Council for American Medical Innovation (CAMI; Washington), during which presenters suggested that the National Institutes of Health be reorganized so as to boost the interface between those involved in basic research and those who put the research into use.

Underlying the discussion was the assumption that a greater emphasis on TR will expand the pipeline for new therapeutics both drugs and devices at FDA, but the topic was not addressed in a particularly thoroughgoing fashion, leaving some to wonder whether there is any prospect that a greater emphasis on TR will appreciably reshape the therapeutic landscape.

Debra Lappin, President of CAMI, said the organization was formed in part to determine "how to protect and sustain America's lead in medical innovation," which "attracts global investors to America."

"We know America is losing its competitive edge," Lappin claimed, adding that the U.S.'s "share of patents ... has sharply declined compared to our foreign partners." She noted that the number of new molecular entities (NMEs) making their way through the Center for Drug Evaluation and Research at FDA has tailed off sharply since 1996, when CDER approved more than 50 NMEs. As is widely known, this is a peak number for the years preceding it, but the number has dropped sharply since then despite ever-growing public- and private-sector investment.

Lappin also made the impact-of-disease-on-GDP argument, asserting, "illness and its costs are disabling our economy."

Alan Lesher, PhD, CEO of the American Association for the Advancement of Science (AAAS; Washington), said "the best way to foster translational research ... is to put together basic and clinical researchers in an almost forced setting" to foster idea generation. He also took a moment to plug a new journal AAAS will soon offer on TR.

However, the psychologies of those who do research at NIH may prove resistant to the idea of sharing observations and, to some extent, intellectual property if patents are at stake. Lesher said "NIH has tried ... to change the mindset in the field to seeing this as a critical aspect of the research continuum." However, the agency has had limited success in that endeavor.

Lesher also pointed out that TR will require more cooperation between industry and researchers, which in turn says something about the current approach to dealing with conflicts of interest. "Conflict of interest means bias," he remarked, but asserted that partnership "does not necessarily mean bias, and if we worry too much about conflict of interest," TR will not produce much.

"I think FDA could also use a little work on its mindset," Lesher continued. He said FDA sees itself as "a guardian of the public health from those who wanted to do things to the American people for profit." Regarding the oft-heard demand for more data from drug and device makers, he said, "rigor is good, but over-rigor is bad." All the same, the panel offered no specific ideas as to how to deal with FDA.

In a discussion of venture philanthropy, Amy Comstock Rick, CEO of the Parkinson's Action Network (Washington), observed, "it has traditionally been the view of disease research ... that if appropriate amounts of money are fed into the pipeline, viable ideas will move through the pipeline at appropriate speeds."

Rick made the argument, however, that there is a gap in the new drug and new device pipeline. At this point in the pipeline an area covering development of prototypes and pre-clinical testing, which she described as the valley of death private-sector investment is lagging because of low expectations of return on investment.

Rick asserted that viable research is sitting idle thanks to this trough, stating that the problem "is getting significantly worse ... in an era of limited resources." She said large pharmaceutical firms are presumed to be willing to pluck the small, venture capital-fed innovators and hence bring new products to market, but "what we're finding is that the venture capital money is drying up," because investors have grown wary of the long developmental timelines. Also, big pharma "is getting more conservative" over time because of the ROI question, she said.

Rick said help may be on the way to the extent that newly appointed NIH director Francis Collins, PhD, has indicated that translational research is one of his top five priorities, but she asserted that Congress ought to get involved. She said NIH is not structured or funded for translational research.

"We believe that the structure of NIH needs to be somewhat realigned so that it can adequately support translational research," Rick said, adding that her organization seeks a piece of legislation that would put an Office of Translational Research into the Office of the Director at NIH.

Lesa Mitchell, of the Ewing Marion Kauffman Foundation (Kansas City, Missouri), said the usual model for therapeutic product development may itself be outdated. "The essence of the problem is thinking of it as a sequential model," she said, expressing a preference for a model that more closely resembles a network in terms of architecture. In this schematic, the role of venture philanthropy will assume a more prominent role than in the past and cross-pollination will be a more prominent driver of innovation.

"The not-for-profit component ... is having to move up the [product development] pipeline," Mitchell said, adding that industry cannot move backward in the pipeline "because their business model is broken." Universities, however, can help fill in this gap.

Mitchell said, "incentive alignment is everything" in the current state of affairs and in any changes that the research community might want to make. "We have to re-look at the incentives," she remarked, making the case that the patent obtained by a university researcher isn't always particularly useful. "The incentives need to be around sharing and collaboration" rather than around individual achievement, she said.